Medical device and method of implanting gastroesophageal anti-reflux and obesity devices in an esophagus

ABSTRACT

A method of preventing contraction and peristaltic wave action of an esophagus in which a GARD is placed, preventing displacement of the GARD towards or into a stomach, the method comprising injecting botulinum toxin very precisely in the muscular layer of the esophageal wall at the level where the GARD is or will be placed. A system comprising a catheter having one or two expandable balloon(s) which carries guide needle catheters that can pierce the esophageal wall and reach precisely the muscular layer of the wall of the esophagus, the needles used to inject the toxin at precisely the exact location in the esophageal wall in relationship with the GARD device to block esophageal peristalsis locally.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Stage Application under 35 U.S.C. §371 of PCT International Application No. PCT/US2018/035312, entitled“MEDICAL DEVICE AND METHOD OF IMPLANTING GASTROESOPHAGEAL ANTI-REFLUXAND OBESITY DEVICES IN AN ESOPHAGUS,” filed on May 31, 2018, whichclaims the benefit of U.S. provisional application No. 62/513,572, filedon Jun. 1, 2017, and 62/629,216, filed on Feb. 12, 2018, which areclaimed and are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

This invention relates to the field of medical devices, particularlymedical devices relating to gastroenterology, and more specifically tomethods of implanting gastroesophageal anti-reflux devices and orobesity devices in an esophagus.

GARDs are thin walled tubular medical devices placed in the esophaguswhich are placed in the esophagus or extend from the esophagus into thestomach with a top ring that is calibrated precisely to the millimeterto the diameter of the esophagus with a calibration basket that ispassed through the working channel of the endoscope at the level of thelower third of the body of the esophagus under visual control of thegastroscope to determine the diameter of the esophagus once opened. Thecalibration basket is opened up to the point where the three arms of thecalibration basket are in contact with the wall of the esophagus, thesize is marked on the handle of the calibration basket, then thecalibration basket is closed, removed from the working channel of thegastroscope and is reopened to the same opening outside the patient. Inorder to determine the appropriate size ring, usually between 20 mm and30 mm of diameter, the calibration basket is reopened to the same sizemeasured in the esophagus and a calibration card with sizing holes isused to determine to the millimeter the size of the GARD device neededfor a given patient.

The Diagnosis and Management GARD (“DM-GARD”) has a tube in the range of5 cm to 10 cm, preferably 7.5 cm, long with a 2.5 cm long ring for atotal length of 7.5 to 12.5 cm, preferably 10 cm, wherein thethin-walled tube will fold onto itself during reflux back-pressure andwill straighten back into the original position spontaneously when theback-pressure stops and is indicated to diagnose gastro-esophagealreflux disease (GERD) not responding to PPIs, defined as “RefractoryGERD.” As the DM-GARD is a mechanical device, all refluxate that isacid, bile, mixed, and/or gastric enzymes that reflux form the stomachinto the esophagus will be blocked while Proton Pump Inhibitors (PPIs)which are widely used to treat GERD will only help to treat acid refluxbut do poorly with other kinds of reflux. Also, we now know that thevolume of reflux is the same when the patients take PPIs even when thecontent is less acid. Up to 30% of patients who have GERD do not respondwell or not at all to PPIs and are diagnosed as having Refractory GERD.These patients have no treatment as they do not respond to PPIs as arule. Surgeons avoid operating on patients who do not respond to PPIs,fearing that the patients will be worse off after surgery as thediagnosis is unclear. Also, about 1% of the population hasLaryngo-Pharyngeal Reflux (LPR) which is reflux content reaching thelarynx causing chronic sore throat, chronic cough, voice changesaffecting quality of life and often careers where oral communication isimportant. In many cases, high dose PPIs corresponding to the double ofa normal 40 mg Nexium (esomeprazole) pill will be prescribed to theseLPR patients for 8 to 12 weeks with no effect on the LPR symptoms.pH-impedance tests can demonstrate reflux in these patients if there ishigh volume but the quality of the refluxate is poorly changed withPPIs, particularly when there is bile reflux. The DM-GARD can beexpected to help these patients when implanted for longer periods oftime as the device is purely mechanical and stops all refluxatemechanically without distinction of pH or volume of the refluxatecontent.

A DM-GARD placed temporarily for less than a month can help the doctorand patient decide if a longer, slightly more invasive device, calledthe Therapeutic GARD, should be placed in a given patient for a muchlonger period of time. The GARD family of devices is the only methodthat allows a trial period with a temporary device, namely the DM-GARD,to help determine if the patient should be managed with the DM-GARD andhelp avoid implanting a device that would not be helpful as can happenin the case of surgery or other non-medication based treatments forGERD. The main difference between the temporary DM-GARD and theTherapeutic GARD is that the DM-GARD has a thicker ring with a nitinolhelical spring as described in U.S. Pat. No. 9,572,701 dated Feb. 21,2017 while the Therapeutic GARD has a much thinner ring that canincorporate in the wall of the esophagus as described in U.S.Provisional application No. 62/629,216 filed Feb. 12, 2018.

The OB-GARD has tubes longer than 7.5 cm, usually from 10 cm to morethan 30 cm and reaching well into the stomach which, in addition ofblocking reflux, will force patients to eat small quantities at thetime, chew their food better, and eat more slowly, leading to earliersatiety as the food passes through the length of the tubes and helpingthe patients to lose weight with appropriate diets. Longer tubesreaching through the stomach can reversibly mimic the second most commonbariatric operation, namely the “sleeve” gastrectomy, where threequarters of the stomach are definitively removed along the greatercurvature of the stomach, leaving a “sleeve” along the lesser curvatureof the stomach. The OB-GARD as the Therapeutic GARD will also have athinner ring capable of integration in the esophageal wall withadditional features and techniques.

The tube of the OB-GARD does not require such surgery as the OB-GARD isplaced through the mouth. To keep the GARD family of devices in place, aring at the top, or proximal end, of the device is placed in the lowerthird of the esophagus, more precisely in the last 5 cm of the esophagusabove the Z line or esogastric junction. The presence or not of a hiatushernia does not affect the use of the GARD family of devices as it canin other endoscopic treatments available. Even longer OB-GARDs goingthrough the stomach into the duodenum and jejunum can be consideredmimicking the effect of the most efficient present bariatric operation,namely the gastric by-pass operation as an internal tube in the duodenumand small bowel would hold the food separately from all the gastric,bowel, bile and pancreatic secretions and enzymes helping the patientlose weight, which is done presently only through major surgery in highrisk morbidly obese patients.

Also, GERD will often appear when patients gain weight. Often as littleas a 5 to 10 pound (approximately 3 kg to 5 kg) can be sufficient tocause severe GERD that will improve with weight loss. The GARD is theonly treatment that addresses both obesity and weight loss.

However, even with very careful sizing of the ring as described above,if the ring is wide enough to keep the GARD in the esophagus, theperistaltic contractions will not automatically push the GARD in thestomach but strong peristaltic contractions of the esophagus immediatelyabove the ring will press hard on the top part of the ring of the GARDand cause ulcers in the esophageal mucosa at the level of the ring orimmediately above as these peristaltic contractions try in vain to pushthe GARD downwards into the stomach. These esophageal ulcers can bleedor lead to perforations. However, above these esophageal ulcers theesophagus is normal.

There is a need to prevent displacement of a GARD from its intendedlocation in the smooth muscle area of the esophagus resulting fromcontractions and peristaltic wave action without causing ulcerations ofthe esophageal mucosa.

SUMMARY OF THE INVENTION

This need is addressed by the present invention which comprises in oneaspect a method of blocking the contractions of the esophagus byinjection of botulinum toxin in the wall of the esophagus just above thelevel where the GARD ring will be placed and thereby decreasing orabolishing the peristalsis of the esophagus in the area of the esophagusabove where the GARD ring will be placed so that a GARD device canremain safely at its intended position for a up to a few months. Inanother aspect the invention comprises a system for delivery of thebotulinum toxin in the wall of the esophagus at the intended location,the system comprising a balloon with a balloon expander orientingguiding tubes for an injection catheter adapted to allow preciseinjection of Botulinum toxin around the circumference of the esophagusat a selected depth in the esophagus to reach the muscular layer of theesophagus. A further aspect is the injection device comprising thecatheter having the balloon arranged to block the catheter centrally inthe esophagus when expanded so that an injection catheter will reach theesophageal wall at a selected angle for injection of the toxin at aselected depth in the muscular layer of the esophagus.

Another important advantage of botulinum toxin injection in thisindication is that it has a temporary effect of at least 2 to 3 months.This is exactly the time needed to assess the efficacy of the DM GARDthat will be placed between 1 week and 4 weeks and then removed. If theDM GARD helps the patient, either the Therapeutic GARD (Th-GARD) can beplaced if one treats GERD or the Obesity GARD (OB-GARD) can be insertedwith no need to reinject any botulinum toxin. The botulinum toxin byblocking locally peristalsis will allow integration of the TherapeuticGARD or the Obesity GARDs in the wall of the esophagus for permanentplacement. As a potential side-effect of botulinum toxin injection canbe some swallowing difficulties, we know that this side-effect istransient even if it turns out with the DM GARD that the patient is nothelped by this therapeutic approach and the plan to place the Th-GARD orOB-GARD is not carried out.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of a portion of human anatomycomprising an esophagus and stomach with a perspective view of a GARDdevice according to the invention, illustrating the position of the GARDdevice in the lower esophagus.

FIG. 2 is an enlarged perspective view of the ring of the GARD and thesites of injection of the botulinum toxin, illustrating a portion of anesophagus in cross-section.

FIG. 3 is a cross-sectional view from above the top of the ring as seenwith the gastroscope placed in the esophagus.

FIG. 4 is a side perspective view of an injection balloon catheter withguiding tubes, before inflation at introduction, partially incross-section.

FIG. 5A is a side perspective view of an injection balloon catheter withthe balloon inflated.

FIG. 5B is a side perspective view of a balloon expander with three armsspread.

FIG. 6 is a side perspective view of an injection balloon catheter withguiding tubes, before inflation, which is a variant of FIG. 4 with atriangular balloon.

FIG. 7 is a side perspective view of the device of FIG. 6 wherein thetriangular balloon is inflated and pushes up the arm of the balloonexpander and the end of the guiding tube.

FIG. 8A is a side perspective view of a GARD Introducer with a Botulinumtoxin injection catheter.

FIG. 8B is a cross-sectional view of the central catheter of FIG. 8A.

FIG. 8C is cross-sectional view of the central catheter of FIG. 8A withfour tubes.

FIG. 9 is a side perspective view of the device of the invention withthreads A,B,C pulled out to release the GARD.

FIG. 10 illustrates the device of FIG. 9 with the A,B,C threadscompletely pulled out of the catheter.

FIG. 11 illustrates a combination of a top small triangular, or conicalballoon 23 used to spread the arms of the arm expander 22 and theguiding tube 18 and a bottom oval balloon 16 to help deploy the ring ofthe GARD.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

Referring first to the drawings which illustrate certain preferredembodiments of the system aspect of the invention, the invention is notlimited to any of the illustrated embodiments.

FIG. 1 shows the position of the GARD device in the lower esophagus 1.The tubular part of the GARD device 4 extends into the stomach 2A, belowa hiatus hernia 2B which is part of stomach 2A sliding above thediaphragm 6 in the lower chest as the chest is above the diaphragm. Aring 3A having a top 3C of the GARD device includes helical spring 3B inthe lower esophagus 1. The level of the Z line 5 is at the junction ofgastric and esophageal mucosa. Diaphragm 6 is shown above stomach 2A.The site 7 of first injections is about 1 cm above the top 3C of theGARD ring. FIG. 1 shows a GARD device which includes a ring 3A whichincludes top 3C and helical spring 3B in the lower esophagus and 3C topof the ring, the ring 3A being placed above the level of the Z line 5,which is shown as an irregular line located just at the junction ofgastric and esophageal mucosa in the lower esophagus 1. The tubular part4 of the GARD device extends into stomach 2A. Diaphragm 6 is locatedbetween the lower part of the hiatus hernia 2B and the stomach 2A. Thesite 7 of the first injections are about 1 cm above the GARD ring 3C.Area of enlargement 8 is shown in FIG. 2 .

FIG. 2 is an enlarged view of the ring 3A of the GARD and the sites 10of injection indicated by arrows 7 of the botulinum toxin in themuscular layer 9 of the wall of the esophagus. Top 3C of ring 3A andhelical spring 3B are illustrated. Mucosa and submucosa 8 and muscularlayer 9 of esophagus 10 are also illustrated. The botulinum toxin isinjected in the muscular layer 9, not in the mucosa or submucosa of theesophagus and not through the wall of the esophagus which is easy to dosince the whole wall is only 2 to 3 mm thick. Injection of the botulinumtoxin has the effect of preventing esophageal peristalsis temporarilyaccording to the invention to assess the efficacy and safety of the GARDdevice and allow the placement of a more permanent device to treatGastroesophageal Reflux Disease (GERD) and/or Obesity.

FIG. 3 is a cross-sectional view above the top of the ring as seen withthe gastroscope placed in the esophagus showing the top 11 of GARD ring3C in upper view, sites 12 of injection right above the GARD ring 3C. Inthis example, the injections sites are at two levels, immediately above12 the ring 11 and 1 cm above 13 the ring 11. Injecting a two levelsinstead of one level is optional. The end 14 of the tubular part of theGARD is seen in perspective.

FIG. 4 illustrates an injection balloon catheter 15 with guiding tubes18 before inflation at introduction. Two guiding tubes 18 are shown onboth sides of the central catheter 17 for the central guide-wire 17A andthe air inflation for the balloon 17B. A third guiding tube is in theback, not shown since hidden by the central part of the catheter 17. Theballoon 16 is not inflated in this view. The tubes 18 act as lumens forguiding tubes for botulinum toxin injection catheters. In FIG. 4 theballoon catheter is placed above and inside the GARD ring to guidebotulinum toxin injection at the right depth and at even distancesaround the circumference of the esophagus. The injection catheter can becombined with the delivery or introduction device used to place the GARDin the esophagus through the mouth as the same balloon helps deploy theGARD ring 3A and insures proper placement of the injection tubes 18needed for precise botulinum toxin injection in the esophageal wall (SeeFIGS. 8A-8C, 9 and 10 ) or two separate catheters can be used, the firstone to introduce the GARD and the second one to inject the botulinumtoxin. Here in FIG. 4 the balloon catheter is separate from the deliveryor introduction device. This catheter is used after the GARD device hasbeen placed in the esophagus. The catheter has a central lumen used toplace the catheter over a central guide wire 17A placed first throughthe mouth and esophagus into the stomach with an endoscope. Once thecatheter is in position determined by distance graduations (not shown),the balloon can be inflated to help deploy the GARD ring as shown inFIG. 5A. Once the balloon has been inflated, the three arms of theballoon expander 22 will be lifted and will push up the distal end ofthe guiding tubes so that the injection catheter 19 placed in theguiding tube 18 can be pushed until the injection catheter makes contactwith the wall of the esophagus 10 at a proper angle. The needle is thendeployed and pierces the wall of the esophagus at the depth needed toreach the muscular layer of the esophagus.

FIG. 5A illustrates an injection balloon catheter 15 with inflatedballoon 16 and guiding tubes 18 for injection. The injection catheter 19includes needle 20 shown in the wall of the esophagus 1. A syringe 21with botulinum toxin is shown ready for injection in the wall of theesophagus 1.

FIG. 5B illustrates a balloon expander 22 with 3 arms spread.

In FIGS. 6 and 7 , a variant is shown, a triangular balloon 23 not yetinflated in FIG. 6 is inflated in FIG. 7 and pushes up the arm 22 of theballoon expander and the end of the guiding tube 18 at a proper angle sothat the injection catheter 19 will reach the esophageal wall and theneedle 20 will penetrate the esophageal wall at the desired depthreaching the esophageal wall of the esophagus.

FIG. 8A illustrates a combination of the delivery catheter or GARDIntroducer with the Botulinum toxin injection catheter wherein GARD ring3D is folded during insertion and held in place with a suture 25A aroundthe ring 3D to keep the ring folded and a knot 24A and thread 25A thatthen penetrates in the central catheter 17 through port 17 c which isthe proximal exit of the thread 25A. In a similar way, the GARD tube 4Bis also folded and held in place with a suture (not shown in the bottomof the drawing) and a knot (not shown in the bottom) that will be pulledout when pulling on 25B at the top of the drawing to the left. Asecurity thread (not shown in the bottom of the drawing) holds bothknots secure and is released by pulling on 25C shown on the top of thedrawing. FIG. 8A is a combination of the delivery catheter or GARDIntroducer with the Botulinum toxin injection catheter. The knot 24Aused is a special knot known as the “draw hitch” that can be releasedsimply by pulling at one end, even at a distance and the knot will bereleased and the thread can be pulled out very easily. The security hasto be pulled out first before the 2 other knots can be released.

FIG. 8B is a transverse cross-sectional view of the central catheter 17,showing a lumen for the central guide wire 17A, lumen 17B for inflationof balloon and 17D is empty for possible future use, lumens for threads25A and 25B and security thread 25C for the deployment threads of theGARD ring and tube. Guiding tubes 18 for the injection catheter areillustrated. (FIG. 8C is a variant of FIG. 8B with a fourth “bean shape”hole, 2 holes 17C and 17E are used for the threads 25A and 25B used todeploy the ring and tube of the GARD device and a security thread 25Cpassing through 17E.) 17B is for inflation/deflation of the oval balloonand 17D is a spare lumen that can be used if needed for inflation of thetriangular balloon, see FIG. 11 , when and if 2 balloons are used.

FIG. 9 shows threads 25A, B, and C pulled out to release the GARD andair injection 17B to inflate the balloon, shown inflated. In FIG. 9 ,the three knots are released, first the security knot 25C then 25A and25B, and the GARD ring expands as well as the tube. The balloon is theninflated 17B to make sure that the GARD ring expands properly andreaches the wall of the esophagus. A gastroscope or fluoroscopy or bothcan be used optionally to check that the GARD ring is properly expanded.

FIG. 10 illustrates threads 25 A, B, and C completely pulled out of thecatheter with balloon 16 inflated and injection catheter 19 in guidingtube 18 with needle 20 drawn to penetrate the esophageal wall muscularlayer 9. Syringe 26 pumps toxin so it is injected through needle 20.This operation is repeated three times in each of the 3 guiding tubesthen the catheter can be rotated and the same operation can be repeatedonce or twice depending on the diameter of the esophagus so that 6infections (for smaller diameter GARDs with a small circumference of thering) up to 9 injections of botulinum toxin (for larger diameter GARDswith a larger circumference of the ring) can be performed at the exactdepth in the muscular layer of the esophagus and at equidistance aroundthe circumference of the esophagus above the deployed GARD ring.

FIG. 11 illustrates a combination of a top small triangular, or conicalballoon 23 used to spread the arms of the arm expander 22 and theguiding tube 18 and a bottom oval balloon 16 to help deploy the ring ofthe GARD. A stopper 30 in the middle of both balloons separates bothballoon and prevents the folded ring (not shown folded) to move upwardswhen the threads are pulled out (see FIG. 10 ) during deployment of thering 3A. The distance between the injection needle and the upper limitof the ring of the GARD should be in the order of 1 cm to 2 cm,preferably 1 cm so the botulinum toxin acts at its best to preventmigration of the GARD ring. If necessary, the oval balloon can bedeflated once the GARD ring is deployed and the device pushed down a fewcentimeters so that the small triangular or rather conical balloon isright above the ring 3A (not shown) and the injection of botulinum areeven closer to the top part of the GARD ring.

Botulinum toxin is a neurotoxic protein produced by the bacteriumClostridium botulinum and related species. It prevents the release ofthe neurotransmitter acetylcholine from axon endings at theneuromuscular junction and thus causes flaccid paralysis of the muscles.Botulinum toxin also paralyzes smooth muscles as well as striatedmuscles.

Botulinum toxin, particularly type A, is already widely used in medicineand sold as BoTox® by Allergan, Dysport® by Ipsen Pharma and Xeomin byMerz Pharmaceuticals for treatment of muscular blockage in the eye forblepharospasm, bladder hyperactivity, cervical dystonia, chronicmigraine, focal limb spasticity, and for face wrinkles.

According to the invention botulinum toxin can be injected in very smallvolumes, in the order of 0.1 ml to 0.4 ml, which is desirable forinjection in a very narrow area of esophageal muscle about 1 mm to 2 mmthick (about 0.04 to 0.08 inches)

To avoid injecting potentially toxic botulinum toxin through the wall ofthe esophagus, an injection device incorporated or clipped on thedelivery system used to place the GARD in the esophagus or anindependent injection device from the catheter used to place the GARD inthe esophagus is used to inject the botulinum toxin around the innercircumference of the esophagus at a precise depth in the wall of theesophagus.

The injection device consists of a balloon that is inflated when inposition with three “guiding” tubes placed at 120 degrees of each otheraround the 360 degree circumference. Once inflated, when the balloon isin contact with the wall of the esophagus, the exact angle of theguiding tube and the wall of the esophagus can be determined preciselyas the end portion of the guiding tubes is glued to the top part of anhexagonal shaped balloon or better placed on an “balloon expander” madeof a ring and 3 “legs” that are spread by the inflated balloon. Aninjection catheter obtained commercially (Olympus Needlemaster™ needles,Boston Scientific Interject™, Cook Medical AcuJect™) is passed throughthe guiding tubes until the catheter reaches the esophageal wall. Sincethe angle between the catheter with the needle and the wall of theesophagus depends on the diameter of the esophagus that conditions thevolume of air used to inflate the balloon and the diameter of the ringof the GARD device used for a given patient, the exact depth ofinjection can be calculated for each diameter of GARD ring and theappropriate catheter with needle length, normally between 3 mm and 6 mmlong can be chosen in advance so as to inject at a 2 mm depth in themuscular layer of the esophagus in order to inject the botulinum toxinblindly through the esophageal wall into the muscular layer of theesophagus, avoiding injections in the mucosa or submucosa that is tooproximally which can cause esophageal mucosal lesions or too deepthrough the wall of the esophagus that can lead to mediastinitis withcases of deaths reported (See Complications of botulinum toxininjections for treatment of esophageal motility disorders, van Hoeij FB, et al., Dis Esophagus 2017 Feb. 1; 30(3):1-5). Also, usingfluoroscopy can help assess the good position of the injection catheterand the depth of the needle in the wall of the esophagus.

The regular disposition every 120 degrees of the guiding tubes allowsinjections at 3 equidistant locations around the circumference of theesophagus. The balloon is then deflated, the catheter turned 40 degreesand then reinflated with 3 more injections. In larger size diameters ofthe GARD ring as in 30 mm, the operation is repeated a third time as thecircumference of the esophagus will be approximately 90 mm so 9injections of 10 units of botulinum toxin for a total of 90 Units isused, while in a smaller 20 mm diameter of GARD, a 60 degree rotationonce with 6 injections is sufficient as the circumference is about 60 mmand 6 injections of 10 to 15 units of botulinum toxin is sufficient.

Botulinum toxin injection into the gastroesophageal junction of theesophagus is used for more than 20 years to treat patients who haveachalasia and non-cardiac chest pain with non-reflux, nonachalasiaspastic esophageal motor disorders and studies have demonstratedefficacy in relieving pain (see “Botulinum toxin for achalasia” byPasricha et al in the Lancet 341:244-245, 1993 and “Treatment of chestpain in patients with noncardiac, nonreflux, nonachalasia spasticesophageal motor disorders using botulinum toxin injection into thegastroesophageal junction by Larry S Miller et al. in the AmericanJournal of Gastroenterology 97, 1640-1646 (2002)).

As Botulinum toxin is a potential toxic compound, the use of aninjection guide to help the endoscopist inject the botulinum toxin atthe selected, right location and at a selected depth to reach themuscular layer of the esophagus mitigates the potential risks ofbotulinum toxin injections.

Also, it is known that botulinum toxin injection will last for up to oneyear which is more than sufficient for the first generation DM-GARD thatwill be used up to 4 weeks then replaced after 1 month by theTherapeutic-GARD and Obesity-GARD that will include features in additionto the botulinum toxin to help keep the devices in place for longerperiods of time.

EP 2729162 B1 assigned to Allergan, Inc., describes treating twoconditions, Diffuse Esophageal Spasm (DES) and “Nutcracker esophagus,”with Botox A injections in the esophagus.

The present invention comprises injecting Botulinum toxin A in themuscular layer of the body of the esophagus right above the ring of theGARD, not all along the length of the esophagus as needed for DES andNutcracker which the procedure described in the Allergan patent.Allergan's patent does not describe using Botox A to prevent migrationof a medical device like the GARD.

Botulinum toxin A will not be used for injections in the esogastricjunction as used in achalasia but exclusively in association withmedical devices to diagnose and treat GERD, LPR and obesity above theesogastric junction in the lower third of the esophagus and preferablyabout 3 cm to 5 cm above the Z line which is the limit of the gastricmucosa and the esophageal mucosa at the esogastric junction.

The balloon element of the system has two functions, first to helpdeploy the GARD ring and stabilize the guiding tubes thanks to theballoon expander before botulinum toxin injection and second to enableexact placement of the delivery catheter with the balloon in the centerof the esophagus which in turn enables appropriate placement of theguiding tubes in the correct direction and right angle to control depthof botulinum toxin injection precisely into the muscular layer of theesophagus that is 2 mm deep while operating at a distance of about 1meter (or about 3 feet) away. The injection is made about 1 cm above theupper ring of the GARD with a purging volume in the catheter ofapproximately one milliliter and a controlled length of the needle of 3mm to 6 mm when taken out of the protection sheath at endoscopy using a21 to 25 gauge needle, preferably a 23 gauge needle, that will reachboth smooth muscle layers of the esophagus to avoid injecting the toxinat another location either too proximally in the mucosa or submucosa ofthe esophagus or too distally beyond the esophagus as the botulinumtoxin can be very toxic even at very low dose.

EXAMPLES

As an example, a total volume of 1 ml of solvent will be used in a100-Unit vial of Botox or Xeomin so that each 0.1 ml of solutioncontains 10 Units of botulinum toxin. Once the catheter is purged withthe solution outside the body of the patient, there should be at least 1ml of the botulinum toxin ready for injection in the syringe afterpurging the catheter with the botulinum solution. At about 1 cm abovethe ring, 0.1 ml to 0.15 ml corresponding to 10 U to 15 U should beinjected at 6 to 9 sites of equal distance around the circumference ofthe esophagus for a total of about 90 units of botulinum toxin. To helpthe endoscopist proceed with the injection, a catheter with 3 injectiontubes will help guide the injection catheter at a pre-determined angleof penetration of the esophageal wall depending on the inflation of theballoon, which will help determine the depth of injection. Also, the useof fluoroscopy can help guarantee injection in the esophageal wall andin the proper muscular layer of the esophageal wall. The preferredbotulinum toxin for injection used is Xeomin by Merz where 1 ml of NaCl0.9% is used to reconstitute the solution then injected in an Olympusendoscopic injection catheter. However, other brands of botulinum toxinscan be used as well as other catheter and dosages.

The present invention, therefore, is well adapted to carry out theobjectives and attain the ends and advantages mentioned, as well asothers inherent therein. While the invention has been depicted anddescribed and is defined by reference to particular embodiments of theinvention, such references do not imply a limitation on the invention,and no such limitation is to be inferred. Consequently, the invention isintended to be limited only by the spirit and scope of the appendedclaims, giving full cognizance to equivalents in all respects.

What is claimed is:
 1. A method of preventing contraction andperistaltic wave action of an esophagus of a patient causingdisplacement of a gastroesophageal anti-reflux device having a ring usedto diagnose and manage refractory Gastroesophageal Reflux Disease (GERD)from an intended location in the esophagus towards or into the stomachcomprising injecting botulinum toxin in the wall of the esophagusimmediately above where the ring will be placed to prevent contractionand peristaltic wave action of the esophagus.
 2. The method of claim 1wherein said device is a first medical device designed for short termplacement, and wherein said method further comprises determining if thefirst medical device functions as intended and then, after thedetermination, replacing the first medical device with a second medicaldevice designed to function for a long term, each of the medical devicesadapted to treat GERD and/or obesity.
 3. The method of claim 1 whereinthe device is placed in the esophagus to treat GERD and/orLaryngo-Pharyngeal Reflux (LPR) in the patient.
 4. The method of claim 1wherein the device is placed in the esophagus to treat obesityassociated with GERD in the patient.
 5. The method of claim 4 whereinthe device is introduced with the ring folded and kept folded with asuture tied with a draw hitch knot which can be untied from a distanceby pulling on a thread of the suture to release the ring so that thering unfolds.
 6. The method of claim 1, wherein the device is used todiagnose and manage GERD after sleeve gastrectomy for obesity.